ABSTRACT: This paper examines the socio-demographic characteristics and the state of sexual health in the US South, a region comprised of 10 states: Alabama, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, Virginia, and West Virginia. The results show that the region is home to 18 percent of the US population, but its residents are statistically significantly more likely to have lower educational attainment and to live in poverty than other US residents. In addition, residents of the US South have poor sexual health compared to their counterparts living in other regions. Teenagers who live in the US South are more likely to get pregnant and have babies than teenagers in other regions. Likewise, the rates of Chlamydia and Gonorrhea among females age 15 - 19 were higher in the US South than elsewhere in the US. This poor sexual health cost the 10 US South states an estimated $2.3 billion in 2008. The paper concludes with a discussion of the sexual health challenges and opportunities in the US South in light of new federal funding streams that allow for the use of evidence-based approaches in sexual health programs.